دورية أكاديمية
PLK1 Inhibition Targets Myc-Activated Malignant Glioma Cells Irrespective of Mismatch Repair Deficiency-Mediated Acquired Resistance to Temozolomide.
العنوان: | PLK1 Inhibition Targets Myc-Activated Malignant Glioma Cells Irrespective of Mismatch Repair Deficiency-Mediated Acquired Resistance to Temozolomide. |
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المؤلفون: | Higuchi F; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Fink AL; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Kiyokawa J; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Miller JJ; Stephen E. and Catherine Pappas Center for Neuro-Oncology, Division of Hematology/Oncology, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts., Koerner MVA; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Cahill DP; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. hwakimoto@mgh.harvard.edu cahill@mgh.harvard.edu., Wakimoto H; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. hwakimoto@mgh.harvard.edu cahill@mgh.harvard.edu. |
المصدر: | Molecular cancer therapeutics [Mol Cancer Ther] 2018 Dec; Vol. 17 (12), pp. 2551-2563. Date of Electronic Publication: 2018 Sep 14. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Association for Cancer Research, Inc Country of Publication: United States NLM ID: 101132535 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-8514 (Electronic) Linking ISSN: 15357163 NLM ISO Abbreviation: Mol Cancer Ther Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research, Inc., c2001- |
مواضيع طبية MeSH: | DNA Mismatch Repair*/drug effects , Drug Resistance, Neoplasm*/drug effects, Cell Cycle Proteins/*antagonists & inhibitors , Glioma/*drug therapy , Glioma/*pathology , Protein Serine-Threonine Kinases/*antagonists & inhibitors , Proto-Oncogene Proteins/*antagonists & inhibitors , Proto-Oncogene Proteins c-myc/*metabolism , Temozolomide/*therapeutic use, Animals ; Biomarkers, Tumor/metabolism ; Cell Cycle Checkpoints/drug effects ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; DNA Damage ; DNA-Binding Proteins/metabolism ; Down-Regulation/drug effects ; Female ; Gene Silencing/drug effects ; Humans ; Mice, Nude ; Mitosis/drug effects ; Protein Kinase Inhibitors/pharmacology ; Protein Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Pteridines/pharmacology ; Temozolomide/pharmacology ; Up-Regulation/drug effects ; Polo-Like Kinase 1 |
مستخلص: | Mismatch repair (MMR) deficiency through MSH6 inactivation has been identified in up to 30% of recurrent high-grade gliomas, and represents a key molecular mechanism underlying the acquired resistance to the alkylating agent temozolomide (TMZ). To develop a therapeutic strategy that could be effective in these TMZ-refractory gliomas, we first screened 13 DNA damage response modulators for their ability to suppress viability of MSH6-inactivated, TMZ-resistant glioma cells. We identified a PLK1 selective inhibitor, Volasertib, as the most potent in inhibiting proliferation of glioblastoma cells. PLK1 inhibition induced mitotic catastrophe, G (©2018 American Association for Cancer Research.) |
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معلومات مُعتمدة: | R01 CA227821 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (BI 6727) 0 (Biomarkers, Tumor) 0 (Cell Cycle Proteins) 0 (DNA-Binding Proteins) 0 (G-T mismatch-binding protein) 0 (Protein Kinase Inhibitors) 0 (Proto-Oncogene Proteins) 0 (Proto-Oncogene Proteins c-myc) 0 (Pteridines) EC 2.7.11.1 (Protein Serine-Threonine Kinases) YF1K15M17Y (Temozolomide) |
تواريخ الأحداث: | Date Created: 20180916 Date Completed: 20190910 Latest Revision: 20231213 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC6279590 |
DOI: | 10.1158/1535-7163.MCT-18-0177 |
PMID: | 30217967 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1538-8514 |
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DOI: | 10.1158/1535-7163.MCT-18-0177 |